跳至主要内容
MedPath Trial logoMedPath TrialMedPath Trial Home
临床试验/NCT01151423
NCT01151423已完成2 期

A Phase II, Single-blind, Randomized, Placebo-controlled Trial to Study the Efficacy and Safety of Anti-von Willebrand Factor Nanobody Administered as Adjunctive Treatment to Patients With Acquired Thrombotic Thrombocytopenic Purpura

Ablynx, a Sanofi company51 个研究点 分布在 13 个国家目标入组 75 人开始时间: 2011年1月1日最近更新:
Share to TwitterShare to FacebookShare to LinkedInShare to Reddit
适应症

试验速览

阶段
2 期
状态
已完成
发起方
入组人数
75
试验地点
51
主要终点
Time-to-response of Treatment Defined by a Confirmed Recovery of Platelets ≥ 150,000/µL
研究概览研究设计入排标准结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This study was a Phase II, single-blind, randomized, placebo-controlled trial to determine whether anti-vWF Nanobody is safe and effective as adjunctive treatment in patients with aTTP.

Patients received either placebo or anti-vWF Nanobody as adjunctive therapy to plasma exchange (PE).

研究设计

研究类型
Interventional
分配方式
Randomized
干预模型
Parallel
主要目的
Treatment
盲法
Single (Participant)

盲法说明

A single-blinded study design was initiated because, in the initial versions of the protocol, the dosing regimen could be adjusted dependent on the results of the Ristocetin Cofactor (RICO) test following the initial dose. Therefore, a double-blind design was not feasible because the results of the RICO test effectively unblinded the Investigator. Single-blind design was maintained due to the objective nature of the primary endpoint.

入排标准

年龄范围
18 Years 至 —（Adult, Older Adult）
性别
All
接受健康志愿者
否

入选标准

  • •18 years of age or older (adults) or aged 12 to < 18 years (adolescents)
  • •Male or female subject, willing to accept an acceptable contraceptive regimen
  • •Subject with a clinical diagnosis of TTP
  • •Requiring PE (one single PE session prior to randomization into the study was allowed)
  • •Subject accessible to follow-up
  • •Subject able to provide signed and dated informed consent and assent (if applicable, for adolescents)

排除标准

  • •Platelet count ≥ 100,000/µL
  • •Severe active infection indicated by sepsis (requirement for pressors with or without positive blood cultures)
  • •Clinical evidence of enteric infection with Escherichia coli 0157 or related organism
  • •Anti-phospholipid syndrome
  • •Diagnosis of disseminated intravascular coagulation (DIC)
  • •Pregnancy or breast-feeding
  • •Hematopoietic stem cell or bone marrow transplantation-associated thrombotic microangiopathy
  • •Known with congenital TTP
  • •Active bleeding or high risk of bleeding
  • •Uncontrolled arterial hypertension
  • •Known chronic treatment with anticoagulant treatment that cannot be stopped safely, including but not limited to:
  • •vitamin K antagonists
  • •heparin or low molecular weight heparin (LMWH)
  • •non-acetyl salicylic acid non-steroidal anti-inflammatory molecules
  • •Severe or life threatening clinical condition other than TTP that would impair participation in the study
  • •Subjects with malignancies resulting in a life expectation of less than 3 months
  • •Subjects with known or suspected bone marrow carcinosis
  • •Subjects who cannot comply with study protocol requirements and procedures
  • •Known hypersensitivity to the active substance or to excipients of the study drug
  • •Severe liver impairment, corresponding to grade 3 toxicity defined by the CTCAE scale. For the key liver parameters, this is defined as follows:
  • •bilirubin > 3 x upper limit of normal (ULN) (needed to differentiate isolated increase in indirect bilirubin due to hemolysis, this was not an exclusion parameter but disease-related)
  • •alanine transaminase (ALT)/ aspartate transaminase (AST) > 5 x ULN
  • •alkaline phosphatase (ALP) > 5 x ULN
  • •gamma-glutamyl transpeptidase (GGT) > 5 x ULN
  • •Severe chronic renal impairment, as defined by glomerular filtration rate < 30 mL/min
  • •Note that the use of another investigational drug or device within 30 days prior to screening was not allowed. Participation in non-interventional/observational studies and registries during the study period was allowed. Participation in another clinical study was not allowed until the end of the follow-up period or within 30 days after the last study treatment in case of early subject withdrawal from the study. Subjects who had already participated in the current study and had either completed the study per protocol or had discontinued prematurely, were not allowed to be re-included.

结局指标

主要结局

Time-to-response of Treatment Defined by a Confirmed Recovery of Platelets ≥ 150,000/µL

时间窗: From the day of first study drug administration up to 30 days after first study drug administration

Time-to-response, defined by the achievement of platelet count response, confirmed at 48 hours after the initial reporting of this response. Platelet response was defined as recovery of platelets ≥ 150,000/µL. This response had to be confirmed at 48 hours after the initial reporting of platelet recovery ≥ 150,000/µL by a de novo measure of platelets ≥ 150,000/µL and lactate dehydrogenase (LDH) ≤ 2x upper limit of normal (ULN) (i.e., 'confirmed platelet response').

次要结局

  • Number of Daily PE Sessions During the Initial Daily PE Period(During the initial daily PE period, with a median (min, max) duration of exposure to study drug of 6 (2, 36) days)
  • Number of Days With at Least One PE Administration During the Total Course of the Study(During the total course of the study (from Screening till the 12-month follow-up [FU] visit))
  • Number of TEAEs and Their Relationship to Study Drug(From the start of the study up to 1 month follow-up)
  • Pharmacodynamics (PD): Ristocetin Cofactor (RICO) Activity Over Time(From the start of the study up to 1 month follow-up (i.e., at Baseline, Days 1 and 2 of daily PE, last day of daily PE, Day 1 after daily PE, Weeks 1, 2, 3, and 4 after daily PE, Days 3 and 7 of FU and at the 1-month FU visit).)
  • The Maximum Number of Consecutive Days Per Subject Where There Was no Interruption of PE During the Initial Daily PE Period(During the initial daily PE period, with a median (min, max) duration of exposure to study drug of 6 (2, 36) days)
  • Number of Treatment-emergent Adverse Events (TEAEs) by Severity(From the start of the study up to 1 month follow-up)
  • Number and Percentage of Subjects With TEAEs by Severity(From the start of the study up to 1 month follow-up)
  • Number of Participants Who Developed Treatment-emergent Anti-Drug Antibodies (ADA)(From the start of the study until last follow-up visit)
  • Pharmacodynamics: Von Willebrand Factor Antigen (vWF:Ag) Over Time(From the start of the study drug up to 1 month follow-up (i.e., at Baseline, Days 1 and 2 of daily PE, last day of daily PE, Day 1 after daily PE, Weeks 1, 2, 3, and 4 after daily PE, Days 3 and 7 of FU and at the 1-month FU visit).)
  • Resolution of Non-focal Neurological Symptoms(From Baseline till the 12-month FU visit)
  • Number of Participants With Resolution of TTP-related Signs or Symptoms(End of daily PE treatment period (median [min, max] duration of exposure to study drug of 6 [2, 36] days), end of study treatment period (median [min, max] duration of exposure to study drug of 36.5 [2, 90] days) and at 1 month follow-up)
  • Mortality(From the start of the study up to 1 month follow-up)
  • Number of PE Related Adverse Events(From the start of the study up to 1 month follow-up)
  • Plasma Concentrations of Caplacizumab(From the start of the study up to 1 month follow-up (i.e., at Baseline, Days 1 and 2 of daily PE, last day of daily PE, Day 1 after daily PE, Weeks 1, 2, 3, and 4 after daily PE, Days 3 and 7 of FU and at the 1-month FU visit).)
  • PD: Coagulation Factor VIII Clotting Activity (FVIII:C) Over Time(From the start of the study up to 1 month follow-up (i.e., at Baseline, Days 1 and 2 of daily PE, last day of daily PE, Day 1 after daily PE, Weeks 1, 2, 3, and 4 after daily PE, Days 3 and 7 of FU and at the 1-month FU visit).)
  • Number and Percentage of Subjects With Complete Remission Following Initial Daily Plasma Exchange (PE)(From the day of first study drug administration up to 30 days after first study drug administration)
  • Number and Percentage of Subjects With Relapse of TTP(Later than 30 days after the last daily PE)
  • Total Volume of Plasma Administered During the Initial Daily PE Period(During the initial daily PE period, with a median (min, max) duration of exposure to study drug of 6 (2, 36) days)
  • Number and Percentage of Subjects With Exacerbations of TTP(Within 30 days of last day of initial daily PE)
  • Number and Percentage of Subjects With PE Related AEs(From the start of the study up to 1 month follow-up)

研究者

发起方
Ablynx, a Sanofi company
申办方类型
Industry
责任方
Sponsor

研究点 (51)

Loading locations...

相似试验

进行中（未招募）
2 期
A Study to Evaluate the Efficacy and Safety of CBL-514 Compared to Placebo in Participants With Dercum's Disease LipomasDercum's Disease
NCT06303570Caliway Biopharmaceuticals Co., Ltd.19
招募中
2 期
A Phase II Study of Ensifentrine in Non-Cystic Fibrosis BronchiectasisNon-cystic Fibrosis Bronchiectasis
NCT06559150Verona Pharma, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA284
已完成
2 期
To Assess the Efficacy and Safety of Ceftriaxone in Patients With Mild to Moderate Parkinson's Disease DementiaParkinson's Disease Dementia
NCT03413384BrainX Corporation100
终止
1 期
Safety, Tolerability and Pharmacodynamics of SYNB1020Cirrhosis
NCT03447730Synlogic23
已完成
2 期
Efficacy and Safety of MM-II for Treatment of Knee Pain in Subjects With Symptomatic Knee OsteoarthritisOsteoarthritis of Knee
NCT04506463Sun Pharmaceutical Industries Limited397